Project Summary/Abstract There is currently a significant need for new non-invasive imaging techniques able to accurately quantify biomarkers for early detection, diagnosis, and quantification of complications in type 1 diabetes (T1D) such as diabetic retinopathy (DR). Physical Sciences Inc. (PSI) proposes to develop an imaging platform based on a new detection arrangement retrofitted to an existing high-resolution retinal imaging platform that includes adaptive optics-assisted scanning laser ophthalmoscopy (AO-SLO) and Optical Coherence Tomography (OCT). The new technique will allow for visualization and quantification of blood vessels structure and nerve bundle arrangement with exquisite details afforded by AO. The proposed detection scheme will be first tested and demonstrated using an existing multimodal AO retinal imager (MAORI) in Phase I and then in Phase II a new MAORI prototype will be developed specifically for imaging particular characteristics of retinal alterations induces by diabetes. Specific biomarkers for T1D complications will be defined based on patient data acquired by our collaborators from Boston Children's Hospital. About 40 patients with different stages of DR will be imaged during the Phase II Program. PSI has a long, successful history of developing and commercializing high-resolution retinal imagers for the ophthalmic research market. PSI and our collaborators have recognized that one of the main impediments in developing a clinical market for AO-SLO's is that there have been few in-depth studies on the medical application of AO imagers for disease diagnosis and tracking the efficacy of treatments. Despite a relatively large number of research publications on the benefits of AO on understanding fundamental aspects of vision, so far AO has not gained traction in the clinical market. However, given the large incidence of neurovascular diseases, it is possible that the proposed application to use high- resolution retinal imaging to investigate the retinal changes due to diabetes will generate significant drive to bring AO closer to the clinical market. Therefore, PSI is requesting funding for developing this technology with a potentially significant impact on vision research and subsequently on the clinical diagnosis and management of DR.